Role of Biomarkers in Drug Development in Oncology

Response evaluation criteria in solid tumors (RECIST) guidelines have been in use for evaluation of results of treatment of cancer in clinical trials since 2000. RECIST is a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, which is used to extrapolate an overall response to treatment. There are some limitations to this approach. For example, trial eligibility and end points based solely on tumor regression are not applicable to the majority of the clinical manifestations of prostate cancers representing all clinical states. PSA-based eligibility and outcomes under RECIST conflict with established reporting standards for the states of a rising PSA and castrate metastatic disease. The clinical manifestations of prostate cancer across multiple disease states are not addressed adequately using the eligibility criteria and outcomes measures defined by RECIST. Treatment effects can be described more precisely if eligibility criteria are adapted to the clinical question being addressed and clinical state under study, focusing on the duration of benefit defined biochemically, radiographically, and/or clinically.

Several candidate biomarkers have the potential to serve as a guide the development of safer and more efficacious drugs. Challenges faced during biomarker discovery as well as during technology and process translation have been reviewed with specific references to protein biomarkers for cancer drug development (Lee et al. 2007).

Biomarkers will provide a better dimension of assessment of response to treatment. Various clinical areas are expected to move toward adoption of biomarkers at different rates but oncology is expected to have the largest gains from biomarkers over the next five to ten years. The reasons for this are as follows:

  • • Cancer is a genetic disease.
  • • Cancer specimens are readily available for testing.
  • • Cancer is life-threatening, creating an urgency to find a treatment solution and a greater willingness to accept risk.
  • • Patients are very sick and often receive a number of drugs in a short time.
  • • Patients have low clinical response rates to treatment.

Biomarkers hold promise for optimization in dosing, adverse event prediction, efficacy evaluation, lead prioritization, and mechanism-of-action profiling of drug candidates. In addition, oncology has a strong pipeline of drugs in development and a number of smaller companies engaged in innovative research. Already, physicians have access to tests that help identify breast cancer patients at low risk for recurrence, who may not benefit from systemic adjuvant therapy. Identifying suitable biomarkers of biologic activity is important when assessing novel anticancer compounds such as angiogenesis inhibitors to optimize the dose and schedule of therapy.

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